2-azido-N-phenylacetamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise to a solution of aniline (5 g, 53.7 mmol) and Et3N (18.7 ml, 134.3 mmol) in dichloromethane (150 ml) at 0° C. under argon. After the completion of reaction (TLC control), the reaction mixture was diluted with dichloromethane (300 ml). The resultant mixture was washed with water, brine and dried. The residue obtained upon evaporation of solvent was taken up in dry DMF (40 ml), added NaN3 (6.15 g, 94.6 mmol) and the resultant mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried. The residue obtained upon evaporation of the solvent was chromatographed over silica gel to afford the azide (6 g, 63%). After the completion of reaction (TLC control) The resultant mixture was washed with water, brine dried The residue obtained upon evaporation of solvent washed with water, brine dried The residue obtained upon evaporation of the solvent was chromatographed over silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise to a solution of aniline (5 g, 53.7 mmol) and Et3N (18.7 ml, 134.3 mmol) in dichloromethane (150 ml) at 0° C. under argon. After the completion of reaction (TLC control), the reaction mixture was diluted with dichloromethane (300 ml). The resultant mixture was washed with water, brine and dried. The residue obtained upon evaporation of solvent was taken up in dry DMF (40 ml), added NaN3 (6.15 g, 94.6 mmol) and the resultant mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried. The residue obtained upon evaporation of the solvent was chromatographed over silica gel to afford the azide (6 g, 63%). After the completion of reaction (TLC control) The resultant mixture was washed with water, brine dried The residue obtained upon evaporation of solvent washed with water, brine dried The residue obtained upon evaporation of the solvent was chromatographed over silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise to a solution of aniline (5 g, 53.7 mmol) and Et3N (18.7 ml, 134.3 mmol) in dichloromethane (150 ml) at 0° C. under argon. After the completion of reaction (TLC control), the reaction mixture was diluted with dichloromethane (300 ml). The resultant mixture was washed with water, brine and dried. The residue obtained upon evaporation of solvent was taken up in dry DMF (40 ml), added NaN3 (6.15 g, 94.6 mmol) and the resultant mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried. The residue obtained upon evaporation of the solvent was chromatographed over silica gel to afford the azide (6 g, 63%). After the completion of reaction (TLC control) The resultant mixture was washed with water, brine dried The residue obtained upon evaporation of solvent washed with water, brine dried The residue obtained upon evaporation of the solvent was chromatographed over silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure, 2-amino-4-hept-6-ynyl-imidazole-1-carboxylic acid tert-butyl ester (0.075 g, 0.270 mmol) was reacted with 2-azido-N-phenyl-acetamide (0.072 g, 0.410 mmol) and afforded 0.050 g (51% yield) of 2-{4-[5-(2-amino-1H-imidazol-4-yl)-pentyl]-[1,2,3]triazol-1-yl}-N-phenyl-acetamide hydrchloride. 1H NMR (400 MHz, CD3OD) 8.53 (s, 1H), 7.59 (d, J=7.6, 2H), 7.31 (t, J=7.2, 2H), 7.11 (t, J=7.2, 1H), 6.50 (s, 1H), 5.62 (s, 2H), 3.96 (s, 1H), 2.89 (bs, 2H), 2.50 (t, J=6.8, 2H), 1.79 (bs, 2H), 1.66 (bs, 2H), 1.45 (bs, 2H); 13C NMR (100 MHz, CD3OD) δ 164.3, 148.6, 139.2, 130.1, 128.9, 125.9, 121.2, 109.8, 55.7, 28.9, 25.3, 24.7; HRMS (ESI), calculated for C18H23N7O (MH+) 353.1964. Found 353.1968.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise to a solution of aniline (5 g, 53.7 mmol) and Et3N (18.7 ml, 134.3 mmol) in dichloromethane (150 ml) at 0° C. under argon. After the completion of reaction (TLC control), the reaction mixture was diluted with dichloromethane (300 ml). The resultant mixture was washed with water, brine and dried. The residue obtained upon evaporation of solvent was taken up in dry DMF (40 ml), added NaN3 (6.15 g, 94.6 mmol) and the resultant mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried. The residue obtained upon evaporation of the solvent was chromatographed over silica gel to afford the azide (6 g, 63%). After the completion of reaction (TLC control) The resultant mixture was washed with water, brine dried The residue obtained upon evaporation of solvent washed with water, brine dried The residue obtained upon evaporation of the solvent was chromatographed over silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium ascorbate (5.4 mg, 27 μmol), tris-(benzyltriazolylmethyl)amine (2.9 mg, 5.5 μmol) and copper sulfate (0.88 mg, 5.5 μmol) were added to a solution of (E)-2-[[3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]amino]-N-(prop-2-ynyl)benzamide (100 mg, 0.27 mmol) and 2-azido-N-phenylacetamide (48 mg, 0.27 mmol) in DMSO (4.0 mL) and water (1.0 mL). The solution was stirred at rt for 16 h and diluted with water. The suspension was filtered and the filter cake was washed with water and dried. The product was recrystallised from acetonitrile and (E)-2-(3-(3,4-dimethoxyphenyl)acrylamido)-N-((1-(2-oxo-2-(phenylamino)ethyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide (127 mg, 86%) was obtained as a colourless solid; mp 189-191° C.; δH (400 MHz, DMSO-d6) 3.77 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 4.59 (d, J=6.8 Hz, 2H, CH2NH), 5.30 (s, 2H, CH2N), 6.79 (d, J=15.6 Hz, 1H, CH═CHCO), 6.96 (d, J5′,6′=8.4 Hz, 1H, H5′), 7.06 (t, J3″,4″=J4″,5″=8.0 Hz, 1H, H4″), 7.15 (t, J3,4=J4,5=8.4 Hz, 1H, H4), 7.23 (dd, J5′,6′=8.4, J2′,6′=1.6 Hz, 1H, H6′), 7.28 (t, J2″,3″=J3″,4″=J4″,5″=J5″,6″=8.0 Hz, 2H, H3″, H5″), 7.37 (d, J2′,6′=1.6 Hz, 1H, H2′), 7.50-7.56 (m, 4H, CH═CHCO, H5, H2″, H6″), 7.78 (d, J3,4=8.0 Hz, 1H, H3), 8.08 (s, 1H, C═CH), 8.57 (d, J5,6=8.0 Hz, 1H, H6), 9.37 (t, J=5.6 Hz, 1H, CH2NH), 10.43 (s, 1H, NHPh), 11.40 (s, 1H, NH); δC (100 MHz, DMSO-d6) 34.9, 40.4, 52.2, 55.5, 55.6, 110.4, 111.5, 119.2, 119.9, 120.7, 120.8, 122.6, 122.7, 123.7, 124.6, 127.3, 128.1, 128.9, 131.9, 138.4, 139.2, 141.5, 144.5, 148.9, 150.6, 164.0, 164.2, 168.3; HRMS (ESI) calculated for C29H28N6O5 [M+Na]+ 563.2013. found 516.2015; vmax 755, 1023, 1259, 1516, 1671, 3262 cm−1. The suspension was filtered the filter cake was washed with water dried The product was recrystallised from acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium ascorbate (28 mg, 140 μmol), tris-(benzyltriazolylmethyl)amine (15 mg, 28 μmol) and copper sulfate (4.5 mg, 28 μmol) were added to a solution of (E)-2-[[3-(3-methoxy-4-propargyloxyphenyl)-1-oxo-2-propenyl]amino]benzoic acid (0.50 g, 1.4 mmol) and 2-azido-N-phenylacetamide (0.25 g, 1.4 mmol) in DMSO (20 mL) and water (5.0 mL). The solution was stirred at rt for 16 h and diluted with water. The suspension was filtered and the filter cake was washed with water and dried. The crude product was recrystallised from acetonitrile to afford (E)-2-[[3-(3-methoxy-4-((1-(2-oxo-2-(phenylamino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1-oxo-2-propenyl]amino]benzoic acid (0.60 g, 80%) as a colourless solid; mp 220-222° C.; δH (400 MHz, DMSO-d6) 3.82 (s, 3H, OCH3), 5.21 (s, 2H, CH2), 5.36 (s, 2H, CH2), 6.80 (d, J=15.6 Hz, 1H, CH═CHCO), 7.08 (t, J=8.0 Hz, 1H, H4″), 7.16 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.21-7.28 (m, 2H, H6′, H5′), 7.39 (s, 1H, H2′), 7.31 (t, J2″,3″=J3″,4″=J4″,5″=J5″,6″=8.0 Hz, 2H, H3″, H5″), 7.56-7.63 (m, 4H, CH═CHCO, H5, H2″, H6″), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.27 (s, 1H, C═CHN), 8.62 (d, J5,6=8.0 Hz, 1H, H6), 10.48 (s, 1H, NH), 11.30 (s, 1H, NH), 13.60 (br s, 1H, CO2H); δC (100 MHz, DMSO-d6) 52.2, 55.6, 61.4, 110.5, 112.9, 116.6, 119.2, 120.1, 120.4, 122.6, 122.8, 123.8, 126.6, 127.6, 129.0, 131.2, 134.1, 138.5, 141.1, 141.7, 142.2, 149.1, 149.4, 164.2, 169.5; HRMS (ESI) calculated for C28H25N5O6 [M+Na]+ 550.1697. found 550.1691; vmax 1239, 1585, 1665, 2605, 3000, 3250 cm−1. The suspension was filtered the filter cake was washed with water dried The crude product was recrystallised from acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise to a solution of aniline (5 g, 53.7 mmol) and Et3N (18.7 ml, 134.3 mmol) in dichloromethane (150 ml) at 0° C. under argon. After the completion of reaction (TLC control), the reaction mixture was diluted with dichloromethane (300 ml). The resultant mixture was washed with water, brine and dried. The residue obtained upon evaporation of solvent was taken up in dry DMF (40 ml), added NaN3 (6.15 g, 94.6 mmol) and the resultant mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried. The residue obtained upon evaporation of the solvent was chromatographed over silica gel to afford the azide (6 g, 63%). After the completion of reaction (TLC control) The resultant mixture was washed with water, brine dried The residue obtained upon evaporation of solvent washed with water, brine dried The residue obtained upon evaporation of the solvent was chromatographed over silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise to a solution of aniline (5 g, 53.7 mmol) and Et3N (18.7 ml, 134.3 mmol) in dichloromethane (150 ml) at 0° C. under argon. After the completion of reaction (TLC control), the reaction mixture was diluted with dichloromethane (300 ml). The resultant mixture was washed with water, brine and dried. The residue obtained upon evaporation of solvent was taken up in dry DMF (40 ml), added NaN3 (6.15 g, 94.6 mmol) and the resultant mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried. The residue obtained upon evaporation of the solvent was chromatographed over silica gel to afford the azide (6 g, 63%). After the completion of reaction (TLC control) The resultant mixture was washed with water, brine dried The residue obtained upon evaporation of solvent washed with water, brine dried The residue obtained upon evaporation of the solvent was chromatographed over silica gel